The molecular vista: current perspectives on molecules and life in the twentieth century

This essay considers how scholarly approaches to the development of molecular biology have too often narrowed the historical aperture to genes, overlooking the ways in which other objects and processes contributed to the molecularization of life. From structural and dynamic studies of biomolecules to cellular membranes and organelles to metabolism and nutrition, new work by historians, philosophers, and STS scholars of the life sciences has revitalized older issues, such as the relationship of life to matter, or of physicochemical inquiries to biology. This scholarship points to a novel molecular vista that opens up a pluralist view of molecularizations in the twentieth century and considers their relevance to current science

Local variation of hashtag spike trains and popularity in Twitter

We draw a parallel between hashtag time series and neuron spike trains. In each case, the process presents complex dynamic patterns including temporal correlations, burstiness, and all other types of nonstationarity. We propose the adoption of the so-called local variation in order to uncover salient dynamics, while properly detrending for the time-dependent features of a signal. The methodology is tested on both real and randomized hashtag spike trains, and identifies that popular hashtags present regular and so less bursty behavior, suggesting its potential use for predicting online popularity in social media.Comment: 7 pages, 7 figure

Targeted Overexpression of Osteoactivin in Cells of Osteoclastic Lineage Promotes Osteoclastic Resorption and Bone Loss in Mice

This study sought to test whether targeted overexpression of osteoactivin (OA) in cells of osteoclastic lineage, using the tartrate-resistant acid phosphase (TRAP) exon 1B/C promoter to drive OA expression, would increase bone resorption and bone loss in vivo. OA transgenic osteoclasts showed ∼2-fold increases in OA mRNA and proteins compared wild-type (WT) osteoclasts. However, the OA expression in transgenic osteoblasts was not different. At 4, 8, and 15.3 week-old, transgenic mice showed significant bone loss determined by pQCT and confirmed by μ-CT. In vitro, transgenic osteoclasts were twice as large, had twice as much TRAP activity, resorbed twice as much bone matrix, and expressed twice as much osteoclastic genes (MMP9, calciton receptor, and ADAM12), as WT osteoclasts. The siRNA-mediated suppression of OA expression in RAW264.7-derived osteoclasts reduced cell size and osteoclastic gene expression. Bone histomorphometry revealed that transgenic mice had more osteoclasts and osteoclast surface. Plasma c-telopeptide (a resorption biomarker) measurements confirmed an increase in bone resorption in transgenic mice in vivo. In contrast, histomorphometric bone formation parameters and plasma levels of bone formation biomarkers (osteocalcin and pro-collagen type I N-terminal peptide) were not different between transgenic mice and WT littermates, indicating the lack of bone formation effects. In conclusion, this study provides compelling in vivo evidence that osteoclast-derived OA is a novel stimulator of osteoclast activity and bone resorption

Exploring concurrency and reachability in the presence of high temporal resolution

Network properties govern the rate and extent of spreading processes on networks, from simple contagions to complex cascades. Recent advances have extended the study of spreading processes from static networks to temporal networks, where nodes and links appear and disappear. We review previous studies on the effects of temporal connectivity for understanding the spreading rate and outbreak size of model infection processes. We focus on the effects of "accessibility", whether there is a temporally consistent path from one node to another, and "reachability", the density of the corresponding "accessibility graph" representation of the temporal network. We study reachability in terms of the overall level of temporal concurrency between edges, quantifying the overlap of edges in time. We explore the role of temporal resolution of contacts by calculating reachability with the full temporal information as well as with a simplified interval representation approximation that demands less computation. We demonstrate the extent to which the computed reachability changes due to this simplified interval representation.Comment: To appear in Holme and Saramaki (Editors). "Temporal Network Theory". Springer- Nature, New York. 201

Peptide YY ablation in mice leads to the development of hyperinsulinaemia and obesity

Aims/hypothesis. Obese people exhibit reduced circulating peptide YY (PYY) levels, but it is unclear whether this is a consequence or cause of obesity. We therefore investigated the effect of Pyy ablation on energy homeostasis. Methods. Body composition, i.p. glucose tolerance, food intake and hypothalamic neuropeptide expression were determined in Pyy knock-out and wild-type mice on a normal or high-fat diet. Results. Pyy knock-out significantly increased bodyweight and increased fat mass by 50% in aged females on a normal diet. Male chow-fed Pyy −/− mice were resistant to obesity but became significantly fatter and glucose-intolerant compared with wild-types when fed a high-fat diet. Pyy knock-out animals exhibited significantly elevated fasting or glucose-stimulated serum insulin concentrations vs wild-types, with no increase in basal or fasting-induced food intake. Pyy knock-out decreased or had no effect on neuropeptide Y expression in the arcuate nucleus of the hypothalamus, and significantly increased proopiomelanocortin expression in this region. Male but not female knock-outs exhibited significantly increased growth hormone-releasing hormone expression in the ventromedial hypothalamus and significantly elevated serum IGF-I and testosterone levels. This sex difference in activation of the hypothalamo–pituitary somatotrophic axis by Pyy ablation may contribute to the resistance of chow-fed male knock-outs to late-onset obesity. Conclusions/interpretation. PYY signalling is important in the regulation of energy balance and glucose homeostasis, possibly via regulation of insulin release. Therefore reduced PYY levels may predispose to the development of obesity, particularly with ageing or under conditions of high-fat feeding

Human immunodeficiency virus: 25 years of diagnostic and therapeutic strategies and their impact on hepatitis B and C virus

The human immunodeficiency virus (HIV) had spread unrecognized in the human population as sexually transmitted disease and was finally identified by its disease AIDS in 1981. Even after the isolation of the causative agent in 1983, the burden and death rate of AIDS accelerated worldwide especially in young people despite the confection of new drugs capable to inhibit virus replication since 1997. However, at least in industrialised countries, this trend could be reversed by the introduction of combination therapy strategies. The design of new drugs is on going; besides the inhibition of the three enzymes of HIV for replication and maturation (reverse transcriptase, integrase and protease), further drugs inhibits fusion of viral and cellular membranes and virus maturation. On the other hand, viral diagnostics had been considerably improved since the emergence of HIV. There was a need to identify infected people correctly, to follow up the course of immune reconstitution of patients by measuring viral load and CD4 cells, and to analyse drug escape mutations leading to drug resistance. Both the development of drugs and the refined diagnostics have been transferred to the treatment of patients infected with hepatitis B virus (HBV) and hepatitis C virus (HCV). This progress is not completed; there are beneficial aspects in the response of the scientific community to the HIV burden for the management of other viral diseases. These aspects are described in this contribution. Further aspects as handling a stigmatising disease, education of self-responsiveness within sexual relationships, and ways for confection of a protective vaccine are not covered

Manovacuometria realizada por meio de traqueias de diferentes comprimentos

Manovacuometry is a simple, fast, and non-invasive test, with maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) obtained to assist respiratory muscle assessment. Currently, there is a wide variety of models and brands of manovacuometers with different trachea diameters and lengths. However, the interference of these models in the measurements obtained by these equipments needs to be investigated. Thus, this study mainly aimed to verify the influence of tracheal length on maximal respiratory pressures (MRP), obtained by an analog manovacuometer, in healthy individuals. Our secondary objective was to verify the correlation between measurements. Fifty individuals, aged 18 to 30, of both sexes, were evaluated by spirometry and manovacuometry. MIP and MEP were performed using tracheas with same internal diameter (0.5 cm) and 30 cm, 60 cm, and 90 cm length. Significantly lower MIP values were observed when comparing a 90 cm trachea to 30 and 60 cm tracheas (Friedman’s ANOVA test and Wilcoxon test with Bonferroni adjustment). Tracheas with 30, 60, and 90 cm length and same diameter did not affect MIP and MEP values, except the 90 cm trachea for MIP values, which may interfere in the physical therapy clinical practice. Further studies are required to analyze the need for standardizing the trachea length used in manovacuometers.La manovacuometría es una prueba sencilla, rápida y no invasiva por la cual se obtienen la presión inspiratoria máxima (PImax) y la presión espiratoria máxima (PEmax), con el objetivo de ayudar en el examen muscular respiratorio. Hoy día se encuentran una gran variedad de modelos y marcas de manovacuometros, con diferentes diámetros y longitudes de las tráqueas, pero hacen falta estudios sobre la interferencia de estos modelos en las mediciones por este instrumento. En este texto se propone examinar en sujetos sanos, en primer lugar, la influencia en la longitud de las tráqueas en las presiones respiratorias máximas, obtenidas por manovacuometros analógicos, y en segundo lugar comprobar la existencia de correlación entre las mediciones. Se evaluaron a cincuenta sujetos entre 18 y 30 años de edad, tanto varones como mujeres, empleando la espirometría y la manovacuometría. Se midió la PImax y la PEmax empleando tráqueas de mismo diámetro interno (0,5 cm) y con longitudes de 30, 60 e 90 cm. Se observaron valores significativamente menores de PImax con la tráquea de longitud de 90 cm en comparación con las PImax con las tráqueas de 30 y 60 cm (prueba de Friedman’s ANOVA, la de Wilcoxon con ajustes de Bonferroni). Las tráqueas de 30, 60 y 90 cm de longitud y mismo diámetro no influyeron en los valores de la PEmax y de la PImax, con excepción de la tráquea de 90 cm en los valores de la PImax, lo que puede interferir la práctica clínica fisioterapéutica. Se necesitan más estudios para evaluar la necesidad de estándares de la longitud de tráqueas empleadas en manovacuometros.A manovacuometria é um teste simples, rápido e não invasivo por meio do qual a pressão inspiratória máxima (PImáx) e a pressão expiratória máxima (PEmáx) são obtidas, a fim de auxiliar na avaliação muscular respiratória. Atualmente, há grande variedade de modelos e marcas de manovacuômetros, com diferentes diâmetros e comprimentos de traqueias, no entanto, a interferência desses modelos nas medidas obtidas por esses equipamentos necessita de investigação. Desta forma, o objetivo primário deste estudo foi verificar a influência do comprimento de traqueias nas pressões respiratórias máximas, obtidas por meio de manovacuômetro analógico, em indivíduos saudáveis e, secundariamente, se há correlação entre as medidas. Foram avaliados 50 indivíduos, de 18 a 30 anos, de ambos os sexos, por meio da espirometria e manovacuometria. As PImáx e PEmáx foram realizadas com uso de traqueias de mesmo diâmetro interno (0,5 cm) e comprimentos de 30, 60 e 90 cm. Foram observados valores significativamente menores de PImáx obtidos com a traqueia de comprimento de 90 cm comparados às PImáx obtidas com as traqueias de 30 e 60 cm (teste de Friedman’s ANOVA com teste de Wilcoxon com ajuste de Bonferroni). As traqueias de 30, 60 e 90 cm de comprimento e mesmo diâmetro não influenciaram os valores de PEmáx e PImáx, exceto a traqueia de 90 cm para os valores de PImáx, o que pode interferir na prática clínica fisioterapêutica. Novos estudos são necessários para analisar a necessidade de padronização do comprimento da traqueia utilizada em manovacuômetros

Bioinformatic and statistical analysis of the optic nerve head in a primate model of ocular hypertension

<p>Abstract</p> <p>Background</p> <p>The nonhuman primate model of glaucomatous optic neuropathy most faithfully reproduces the human disease. We used high-density oligonucleotide arrays to investigate whole genome transcriptional changes occurring at the optic nerve head during primate experimental glaucoma.</p> <p>Results</p> <p>Laser scarification of the trabecular meshwork of cynomolgus macaques produced elevated intraocular pressure that was monitored over time and led to varying degrees of damage in different samples. The macaques were examined clinically before enucleation and the myelinated optic nerves were processed post-mortem to determine the degree of neuronal loss. Global gene expression was examined in dissected optic nerve heads with Affymetrix GeneChip microarrays. We validated a subset of differentially expressed genes using qRT-PCR, immunohistochemistry, and immuno-enriched astrocytes from healthy and glaucomatous human donors. These genes have previously defined roles in axonal outgrowth, immune response, cell motility, neuroprotection, and extracellular matrix remodeling.</p> <p>Conclusion</p> <p>Our findings show that glaucoma is associated with increased expression of genes that mediate axonal outgrowth, immune response, cell motility, neuroprotection, and ECM remodeling. These studies also reveal that, as glaucoma progresses, retinal ganglion cell axons may make a regenerative attempt to restore lost nerve cell contact.</p